Although testicular cancer (TC) treatment has been associated with severe late morbidities, including second malignant neoplasms (SMNs) and ischemic heart disease (IHD), cause-specific excess mortality has been rarely studied among patients treated in the platinum era.
In a large, multicenter cohort including 6042 patients with TC treated between 1976 and 2006, cause-specific mortality was compared with general population mortality rates. Associations with treatment were assessed with proportional hazards analysis.
With a median follow-up of 17.6 years, 800 patients died; 40.3% of these patients died because of TC. The cumulative mortality was 9.6% (95% confidence interval [CI], 8.5%-10.7%) 25 years after TC treatment. In comparison with general population mortality rates, patients with nonseminoma experienced 2.0 to 11.6 times elevated mortality from lung, stomach, pancreatic, rectal, and kidney cancers, soft-tissue sarcomas, and leukemia; 1.9-fold increased mortality (95% CI, 1.3-2.8) from IHD; and 3.9-fold increased mortality (95% CI, 1.5-8.4) from pneumonia. Seminoma patients experienced 2.5 to 4.6 times increased mortality from stomach, pancreatic, bladder cancer and leukemia. Radiotherapy and chemotherapy were associated with 2.1 (95% CI, 1.8-2.5) and 2.5 times higher SMN mortality (95% CI, 2.0-3.1), respectively, in comparison with the general population. In a multivariable analysis, patients treated with platinum-containing chemotherapy had a 2.5-fold increased hazard ratio (HR; 95% CI, 1.8-3.5) for SMN mortality in comparison with patients without platinum-containing chemotherapy. The HR for SMN mortality increased 0.29 (95% CI, 0.19-0.39) per 100 mg/m2 platinum dose administered (Ptrend < .001). IHD mortality was increased 2.1-fold (95% CI, 1.5-4.2) after platinum-containing chemotherapy in comparison with patients without platinum exposure.
Platinum-containing chemotherapy is associated with a dose-dependent increase in the risk of SMN mortality.
Cancer. 2019 Nov 15 [Epub ahead of print]
Harmke J Groot, Flora E van Leeuwen, Sjoukje Lubberts, Simon Horenblas, Ronald de Wit, J Alfred Witjes, Gerard Groenewegen, Philip M Poortmans, Maarten C C M Hulshof, Otto W M Meijer, Igle J de Jong, Hetty A van den Berg, Tineke J Smilde, Ben G L Vanneste, Maureen J B Aarts, Katarzyna Jóźwiak, Alexandra W van den Belt-Dusebout, Jourik A Gietema, Michael Schaapveld
Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands., Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Department of Urology, Radboud University Medical Center, Nijmegen, the Netherlands., Department of Medical Oncology, Cancer Center, University Medical Center Utrecht, Utrecht, the Netherlands., Department of Radiation Oncology, Dr. Bernard Verbeeten Institute, Tilburg, the Netherlands., Department of Radiation Oncology, Academic Medical Center, Amsterdam, the Netherlands., Department of Radiation Oncology, VU University Medical Center Amsterdam, Amsterdam, the Netherlands., Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Department of Radiotherapy, Catharina Hospital, Eindhoven, the Netherlands., Department of Medical Oncology, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands., Department of Radiotherapy, Maastro Clinic, Maastricht, the Netherlands., Department of Medical Oncology, Maastricht University Medical Center, Maastricht, the Netherlands., Department of Biostatistics, Netherlands Cancer Institute, Amsterdam, the Netherlands.